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Physiology of Aging

Introduction

  • Aging = complex, multifactorial; nutrition is major determinant from pre-conception onward.
    • Key interactive domains: genetics, health behaviours, lifestyle/environment, medical conditions.
    • TABLE 2-1 cross-links physiologic changes with nutrient needs. Selected examples:
    • ↓ muscle mass → ↓ energy need + ↑ need for high-quality protein
    • Atrophic gastritis, ↑ gastric pH → ↑ need for vitamins B6,B{12},K, folate, Ca, Fe, Zn
    • ↓ skin vitamin D synthesis + renal activation → ↑ need for Ca & D.
  • Normal/physiologic aging (senescence) ≠ pathology, yet reduces functional reserve → ↑ vulnerability to disease.

Theories of Aging

  • Two broad, inter-connected categories:
    • Programmed theories
    • Life span genetically pre-set; cellular "biologic clock".
    • Telomere shortening:
      • Telomere = protective non-coding DNA cap; each replication shortens length.
      • When too short → loss of chromosomal protection → apoptosis/senescence.
      • Short telomeres correlate with shorter life span & ↑ chronic disease risk; heritable, longer in women.
    • Error/Damage theories
    • Cumulative environmental insults create cellular deterioration.
    • Free-radical/ROS theory: mitochondrial respiration → ROS → DNA/protein/lipid oxidation → mutations, dysfunction, death.

The Role of Cell Replication & DNA Stability

  • Accurate DNA replication (≈ 3\times10^{9} base pairs/cell division) essential for longevity.
  • DNA repair proteins correct mismatches; capacity declines with age → mutation accumulation.

Genetics vs. Environment

  • Centenarian data: avg. centenarian often in better health than avg. 80-yr-old.
    • Lifespan variance ≈ 20–30 % genetic, 70–80 % environmental/epigenetic.
  • Longevity-linked genes: PON1, FOXO variants, etc. interplay with diet, PA, BMI, smoking.

Epigenetics

  • Epigenetics = heritable gene-expression changes without DNA-sequence alteration (e.g., DNA methylation).
    • Methylation patterns correlate with "epigenetic age".
    • Potential reversibility via diet, lifestyle → target for delaying age-related diseases.

Calorie Restriction (CR)

  • Only universal life-span-extending intervention across species.
    • Typical protocol: 15–40 % energy reduction without malnutrition.
    • Mechanisms: slowed DNA methylation drift, lower oxidative damage, ↑ energy efficiency.
    • Human RCT: 15 % CR × 2 yrs → ↓ resting metabolic rate & oxidative stress → supports "rate-of-living" theory.
    • Research into CR mimetics (e.g., resveratrol, metformin, rapalogs).

Whole-Body Physiologic Summary (Table 2-2 highlights)

  • ↓ lean body mass, ↑ adiposity until 60 y then fat ↓; drug distribution changes.
  • ↓ dopaminergic receptors → parkinsonian traits.
  • Sensory losses: presbyopia, presbycusis, taste/smell decline.
  • ↓ renal blood flow & GFR; ↓ hepatic P-450; ↓ baroreflexes; ↓ vital capacity & ↑ residual volume.

Gastrointestinal Changes

  • Oral health
    • First signs of malnutrition show in oral tissues; xerostomia (often drug-induced) raises caries risk.
    • Poor dentition/dentures → limited food choices, social withdrawal.
  • Sensory decline
    • Taste buds ↓ after 40–60 y; salty/sweet lost first. Olfactory impairment in 62–75 % ≥80 y.
    • Consequences: anorexia of aging, over-salting, food safety issues.
  • Esophagus
    • Dysphagia prevalence 15–35 % elders; due to neuro diseases, sarcopenia, meds (opioids, anticholinergics).
    • Complications: aspiration pneumonia, dehydration, weight loss.
  • Stomach & SI
    • Delayed gastric emptying → post-prandial hypotension, GERD.
    • Atrophic gastritis + H. pylori ↑: ↓ HCl & IF → B_{12} malabsorption.
    • Pancreatic enzyme output & bile ↓ → fat malabsorption & ADEK deficits.
  • LI
    • Transit slows; constipation common multifactorial (↓ fiber, fluids, mobility, meds).

Body Composition Changes

  • Weight: rises till ~60 y then plateaus/declines.
  • Sarcopenia: loss of muscle mass & strength (8–40 % ≥60 y; >50 % ≥75 y).
    • Drivers: anabolic resistance, inactivity, inflammation, hormonal shifts, inadequate protein.
    • Intervention: ≥1.0-1.2\,g\,protein\,kg^{-1}, leucine-rich sources, resistance training, antioxidants.
  • Sarcopenic Obesity: coexistence of high fat + low muscle → compounded disability, insulin resistance.
  • Intentional weight loss may exacerbate muscle loss—must combine with exercise + protein.

Cardiovascular & Respiratory Changes

  • Cardiovascular aging
    • Structural: arterial stiffening, endothelial dysfunction, LV wall thickening, ↓ max HR & VO2 max.
    • Atherosclerosis develops over decades; influenced strongly by diet/PA.
  • Modifiable dietary risk factors (Table 2-4)
    • \uparrow SFA/TFA & cholesterol ↑ LDL; soluble fiber, sterols, MUFA/PUFA ↓ LDL.
    • Excess refined CHO, ETOH, obesity ↑ TG & ↓ HDL.
  • AHA 2020 ideal health metrics: smoke-free, BMI<25, PA ≥150 min/wk, DASH-like diet, optimal BP, lipids, glucose.
  • Hypertension: pre-HTN 120\le SBP \le139\,mmHg or 80\le DBP \le89\,mmHg doubles risk → lifestyle & DASH.
  • Lungs: ↓ elastic recoil, ↓ vital capacity, ↑ residual volume; immune decline ↑ pneumonia risk.

Renal System

  • Peak renal mass in 40s; by 60 y average 25 % function lost.
    • Annual GFR drop ≈ 0.75\,mL\,min^{-1}\,1.73m^{-2}.
    • CKD defined as GFR < 60\,mL\,min^{-1}\,1.73m^{-2} ≥3 months.
  • Contributors: diabetes, HTN, CVD, obesity, nephrotoxic drugs.
  • Aging GU tract: bladder capacity ↓, prostate hypertrophy, pelvic floor laxity → incontinence → voluntary fluid restriction → dehydration.

Skeletal Health

  • Peak bone mass ~late 20s; 50–90 % genetically set, remainder diet + activity.
  • Hormonal regulators: PTH, calcitonin, GH/IGF-1, cortisol, vitamin D.
  • Vitamin D synthesis ↓ in skin & renal activation; combined with low intake → poor Ca absorption.
  • Osteoporosis
    • Microarchitectural deterioration; common fracture sites spine, hip, wrist.
    • Primary (age/post-menopause) vs Secondary (drugs e.g., glucocorticoids, PPIs).
    • Nutrition essentials (Table 2-7): Ca 1200\,mg/d, vitamin D 800–1000\,IU/d, vit K, Mg, protein (but not excessive), ω-3, antioxidants.
    • Excess Na, P (cola), vitamin A, alcohol, caffeine can leach bone.
    • Weight-bearing & balance exercise reduce falls—the largest fracture modulator.

Immune, Nervous, Endocrine, Hematologic Changes

  • Immunosenescence
    • ↓ naïve T & B cells, ↓ vaccine response, ↑ inflammatory cytokines.
    • Nutrition link: deficits in protein, vitamins A, C, D, E, B6, B{12}, folate, Zn, Se impair immunity; probiotics & ω-3 may modulate.
    • Moderate PA boosts adaptive immunity.
  • Nervous system
    • Brain volume ↓, neurotransmitter synthesis ↓; slower processing, sensory losses.
    • Nutrients impacting cognition/mood: B-complex (folate, B6,B{12}), vit D, ω-3 (DHA), antioxidants (vit C, E, carotenoids).
  • Endocrine
    • ↓ sex steroids, GH/IGF-1, thyroid hormones; ↑ insulin resistance.
    • Influence on sarcopenia, osteoporosis, metabolic syndrome.
  • Anemia in Elders
    • Prevalence >20 % ≥85 y. Three equal etiologies:
    • Nutritional (Fe, B_{12}, folate)
    • Anemia of inflammation/CKD/chronic disease (hepcidin-mediated Fe sequestration)
    • Unexplained (possible cytokine or other micronutrient effects)
    • Iron-deficiency often due to occult GI bleed.
    • Work-up includes diet review, meds (acid suppressors), renal function; treatment may require combined nutrition + medical approaches.

Practical / Food-Service Perspectives

  • Culture-Change movement → resident-directed meals, liberalized diets, restaurant-style menus, CDM oversight.
  • Danger of over-restrictive diets (e.g., low Na) in elders: palatability ↓ → unintended weight loss & malnutrition.
    • Need individualized, least-restrictive approach.
  • LET’S DISCUSS exercises: beverage sugar cube demo; curate credible senior health websites; craft social-media messages.

Key Study Data & Numbers

  • Centenarians worldwide 2015 ≈ 5\times10^{5}; projected 2050 3.7\,million.
  • US centenarians up 43.6 % 2000–2014 (50,281 → 72,197).
  • Immunologic decline starts ≈50 y; olfactory loss in 62–75 % ≥80 y.
  • Dysphagia prevalence 15–35 % institutional elders; 11.4 % community dwelling.
  • Obesity in ≥65 y: >30 %; Sarcopenia affects 8–40 % ≥60 y.

Ethical / Practical Implications

  • Balancing disease-oriented restrictions with quality of life; respect autonomy (culture change).
  • Equity in access: socioeconomic & functional barriers to nutrient-dense foods.
  • Research gaps: epigenetic diet modulation, CR mimetics, anemia of unexplained origin.

Connections to Foundational Principles

  • Homeostasis: Aging reduces reserve → nutrition acts as buffer.
  • Rate-of-Living & oxidative stress theories linked to antioxidant nutrient needs.
  • Systems biology: gastro, renal, hepatic, endocrine interact—drug/nutrient interplay.

Formulae & Clinical Cut-offs (selected)

  • Telomere attrition per mitosis \approx 50–200\,bp
  • CKD: \text{GFR}
  • Pre-HTN: 120\le SBP<140 mmHg OR 80\le DBP<90 mmHg.
  • Protein for sarcopenia: 1.0–1.2\,g\,kg^{-1}\,day^{-1} (may ↑ to 1.5 g in illness).
  • Calorie restriction research range: 15–40\,\% energy deficit.

Key Terms (as per chapter)

  • Senescence, Dysphagia, Dyspepsia, Gustatory dysfunction, Olfaction, Immunosenescence, Sarcopenia, Sarcopenic obesity, DNA methylation, Epigenetics.